237 research outputs found

    Indo-European Language Family Genealogical Relations

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    All the languages that originated in the world have a very long history. A conception of language and the nation emerged among European thinkers engaged in research on the origin of language. This study presents ideas about language and the nation that all the languages of the world have some sort of branching relationship and includes certain commonalities as a family language. This thought identified Indian languages as having a genealogical relationship. They believed that Indian languages could be associated with European languages. The idea of language and nation faced serious challenges when confronting the traditional languages of India. The Tamil language is no exception. Nevertheless, in an attempt to counter it, the Europeans are observing the changes in the Tamil language. The development of the print media, the written transformation of the Tamil language, and the prose character of the Tamil language have played a very important role in the modern invasion of the Tamil language. The thought of the language and the nation of the Europeans have played a very important role. This article is a brief study of the subject

    siRNA knockdown of SPHK1 in vivo protects mice from systemic, type-I Allergy.

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    Systemic anaphylaxis is considered to be a typical immediate hypersensitivity response, determined by the activation of immune cells,
via antigen-induced aggregation of IgE-sensitized FcεRI cells. Perhaps most the important cells, in the immediate hypersensitivity responses, are mast cells. We have previously shown that SPHK1 plays a key role in the intracellular signaling pathways triggered by FceRI aggregation on human
mast cells. More recently, we performed a genome-wide gene expression profiling of human mast cells, sensitized with IgE alone, or stimulated by FcεRI aggregation. We found that sphingosine kinase 1 (SPHK1) was one
of genes activated at the earlier stages of mast cell activation, including during sensitization. Moreover, SPHK1 has been shown, by us and others, to be a key player in the intracellular signaling pathways triggered by
several immune-receptors, including fMLP, C5a, and Fcg- and Fcereceptors. Here we have investigated the in vivo role of SPHK1 in allergy, using a specific siRNA to knockdown SPHK1 in vivo. Our results support a role for
SPHK1 in the inflammatory responses that share clinical, immunological, and histological features of type I hypersensitivity. Thus, mice pretreated with the siRNA for SPHK1 were protected from the IgE mediated allergic
reactions including: temperature changes, histamine release, cytokine production, cell-adhesion molecule expression, and immune cell infiltration into the lungs

    Successful transition from fed-batch to continuous manufacturing within a mAb process development cycle

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    Please click Additional Files below to see the full abstract

    Comparative genomic hybridizations reveal absence of large Streptomyces coelicolor genomic islands in Streptomyces lividans

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    <p>Abstract</p> <p>Background</p> <p>The genomes of <it>Streptomyces coelicolor </it>and <it>Streptomyces lividans </it>bear a considerable degree of synteny. While <it>S. coelicolor </it>is the model streptomycete for studying antibiotic synthesis and differentiation, <it>S. lividans </it>is almost exclusively considered as the preferred host, among actinomycetes, for cloning and expression of exogenous DNA. We used whole genome microarrays as a comparative genomics tool for identifying the subtle differences between these two chromosomes.</p> <p>Results</p> <p>We identified five large <it>S. coelicolor </it>genomic islands (larger than 25 kb) and 18 smaller islets absent in <it>S. lividans </it>chromosome. Many of these regions show anomalous GC bias and codon usage patterns. Six of them are in close vicinity of tRNA genes while nine are flanked with near perfect repeat sequences indicating that these are probable recent evolutionary acquisitions into <it>S. coelicolor</it>. Embedded within these segments are at least four DNA methylases and two probable methyl-sensing restriction endonucleases. Comparison with <it>S. coelicolor </it>transcriptome and proteome data revealed that some of the missing genes are active during the course of growth and differentiation in <it>S. coelicolor</it>. In particular, a pair of methylmalonyl CoA mutase (<it>mcm</it>) genes involved in polyketide precursor biosynthesis, an acyl-CoA dehydrogenase implicated in timing of actinorhodin synthesis and <it>bldB</it>, a developmentally significant regulator whose mutation causes complete abrogation of antibiotic synthesis belong to this category.</p> <p>Conclusion</p> <p>Our findings provide tangible hints for elucidating the genetic basis of important phenotypic differences between these two streptomycetes. Importantly, absence of certain genes in <it>S. lividans </it>identified here could potentially explain the relative ease of DNA transformations and the conditional lack of actinorhodin synthesis in <it>S. lividans</it>.</p

    Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome

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    BACKGROUND: Severe acute respiratory syndrome (SARS) emerged in later February 2003, as a new epidemic form of life-threatening infection caused by a novel coronavirus. However, the immune-pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we investigated the gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from SARS patients, and compared with healthy controls. RESULTS: The number of differentially expressed genes was found to be 186 under stringent filtering criteria of microarray data analysis. Several genes were highly up-regulated in patients with SARS, such as, the genes coding for Lactoferrin, S100A9 and Lipocalin 2. The real-time PCR method verified the results of the gene array analysis and showed that those genes that were up-regulated as determined by microarray analysis were also found to be comparatively up-regulated by real-time PCR analysis. CONCLUSIONS: This differential gene expression profiling of PBMCs from patients with SARS strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection, as we observed a complete lack of cytokine genes usually triggered during a viral infection. Our study shows for the first time how the immune system responds to the SARS infection, and opens new possibilities for designing new diagnostics and treatments for this new life-threatening disease

    Genome-wide transcriptome analysis reveals that a pleiotropic antibiotic regulator, AfsS, modulates nutritional stress response in Streptomyces coelicolor A3(2)

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    <p>Abstract</p> <p>Background</p> <p>A small "sigma-like" protein, AfsS, pleiotropically regulates antibiotic biosynthesis in <it>Streptomyces coelicolor</it>. Overexpression of <it>afsS </it>in <it>S. coelicolor </it>and certain related species causes antibiotic stimulatory effects in the host organism. Although recent studies have uncovered some of the upstream events activating this gene, the mechanisms through which this signal is relayed downstream leading to the eventual induction of antibiotic pathways remain unclear.</p> <p>Results</p> <p>In this study, we employed whole-genome DNA microarrays and quantitative PCRs to examine the transcriptome of an <it>afsS </it>disruption mutant that is completely deficient in the production of actinorhodin, a major <it>S. coelicolor </it>antibiotic. The production of undecylprodigiosin, another prominent antibiotic, was, however, perturbed only marginally in the mutant. Principal component analysis of temporal gene expression profiles identified two major gene classes each exhibiting a distinct coordinate differential expression pattern. Surprisingly, nearly 70% of the >117 differentially expressed genes were conspicuously associated with nutrient starvation response, particularly those of phosphate, nitrogen and sulfate. Furthermore, expression profiles of some transcriptional regulators including at least two sigma factors were perturbed in the mutant. In almost every case, the effect of <it>afsS </it>disruption was not observed until the onset of stationary phase.</p> <p>Conclusion</p> <p>Our data suggests a comprehensive role for <it>S. coelicolor </it>AfsS as a master regulator of both antibiotic synthesis and nutritional stress response, reminiscent of alternative sigma factors found in several bacteria.</p

    Return and Volatility Spillovers of Asian Pacific Stock Markets’ Energy Indices

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    The aim of the study was to investigate the presence of volatility among the Energy Indices of Asia Pacific Stock Markets. To test the volatility among the daily returns of Energy Indices of Asia Pacific Stock Markets, the study selected five sample Asian Pacific stock markets’ Energy Indices on the basis of availability of data. The findings of descriptive statistics and the ADF Test revealed, that the daily returns of the sample energy indices of Asian Pacific stock markets were not normally distributed and achieved stationarity at level difference, over the research period. Hence the data may be used for additional analysis. The data were then analysed, by using the GARCH (1,1) model to assess the considerable volatility of daily returns of sample energy indices and the study, which revealed that during the study period, all of the sample energy indices were volatile

    Genome-wide inference of regulatory networks in Streptomyces coelicolor

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    Background: The onset of antibiotics production in Streptomyces species is co-ordinated with differentiation events. An understanding of the genetic circuits that regulate these coupled biological phenomena is essential to discover and engineer the pharmacologically important natural products made by these species. The availability of genomic tools and access to a large warehouse of transcriptome data for the model organism, Streptomyces coelicolor, provides incentive to decipher the intricacies of the regulatory cascades and develop biologically meaningful hypotheses. Results: In this study, more than 500 samples of genome-wide temporal transcriptome data, comprising wild-type and more than 25 regulatory gene mutants of Streptomyces coelicolor probed across multiple stress and medium conditions, were investigated. Information based on transcript and functional similarity was used to update a previously-predicted whole-genome operon map and further applied to predict transcriptional networks constituting modules enriched in diverse functions such as secondary metabolism, and sigma factor. The predicted network displays a scale-free architecture with a small-world property observed in many biological networks. The networks were further investigated to identify functionally-relevant modules that exhibit functional coherence and a consensus motif in the promoter elements indicative of DNA-binding elements. Conclusions: Despite the enormous experimental as well as computational challenges, a systems approach for integrating diverse genome-scale datasets to elucidate complex regulatory networks is beginning to emerge. We present an integrated analysis of transcriptome data and genomic features to refine a whole-genome operon map and to construct regulatory networks at the cistron level in Streptomyces coelicolor. The functionally-relevant modules identified in this study pose as potential targets for further studies and verification.
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